@article{6931cf7f3a7f482a805614ad1fceee9f,
title = "A saturated map of common genetic variants associated with human height",
abstract = "Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.",
keywords = "Humans, Body Height/genetics, Gene Frequency/genetics, Genome, Human/genetics, Genome-Wide Association Study, Haplotypes/genetics, Linkage Disequilibrium/genetics, Polymorphism, Single Nucleotide/genetics, Europe/ethnology, Sample Size, Phenotype, Chromosome Mapping",
author = "Lo{\"i}c Yengo and Sailaja Vedantam and Eirini Marouli and Julia Sidorenko and Eric Bartell and Saori Sakaue and Marielisa Graff and Eliasen, {Anders U} and Yunxuan Jiang and Sridharan Raghavan and Jenkai Miao and Arias, {Joshua D} and Graham, {Sarah E} and Mukamel, {Ronen E} and Spracklen, {Cassandra N} and Xianyong Yin and Shyh-Huei Chen and Teresa Ferreira and Highland, {Heather H} and Yingjie Ji and Tugce Karaderi and Kuang Lin and Kreete L{\"u}ll and Malden, {Deborah E} and Carolina Medina-Gomez and Moara Machado and Amy Moore and Sina R{\"u}eger and Xueling Sim and Scott Vrieze and Ahluwalia, {Tarunveer S} and Masato Akiyama and Allison, {Matthew A} and Marcus Alvarez and Andersen, {Mette K} and Alireza Ani and Vivek Appadurai and Liubov Arbeeva and Seema Bhaskar and Bielak, {Lawrence F} and Sailalitha Bollepalli and Bonnycastle, {Lori L} and Jette Bork-Jensen and Bradfield, {Jonathan P} and Yuki Bradford and Braund, {Peter S} and Brody, {Jennifer A} and Burgdorf, {Kristoffer S} and Cade, {Brian E} and Hui Cai and Qiuyin Cai and Archie Campbell and Marisa Ca{\~n}adas-Garre and Eulalia Catamo and Jin-Fang Chai and Xiaoran Chai and Li-Ching Chang and Yi-Cheng Chang and Chien-Hsiun Chen and Alessandra Chesi and Choi, {Seung Hoan} and Ren-Hua Chung and Massimiliano Cocca and Concas, {Maria Pina} and Christian Couture and Gabriel Cuellar-Partida and Rebecca Danning and Daw, {E Warwick} and Frauke Degenhard and Delgado, {Graciela E} and Alessandro Delitala and Ayse Demirkan and Xuan Deng and Poornima Devineni and Alexander Dietl and Maria Dimitriou and Latchezar Dimitrov and Rajkumar Dorajoo and Ekici, {Arif B} and Engmann, {Jorgen E} and Zammy Fairhurst-Hunter and Aliki-Eleni Farmaki and Faul, {Jessica D} and Juan-Carlos Fernandez-Lopez and Lukas Forer and Margherita Francescatto and Sandra Freitag-Wolf and Christian Fuchsberger and Galesloot, {Tessel E} and Yan Gao and Zishan Gao and Frank Geller and Olga Giannakopoulou and Franco Giulianini and Gjesing, {Anette P} and Anuj Goel and Gordon, {Scott D} and Mathias Gorski and Jakob Grove and Xiuqing Guo and Stefan Gustafsson and Jeffrey Haessler and Hansen, {Thomas F} and Havulinna, {Aki S} and Haworth, {Simon J} and Jing He and Nancy Heard-Costa and Prashantha Hebbar and George Hindy and Ho, {Yuk-Lam A} and Edith Hofer and Elizabeth Holliday and Katrin Horn and Hornsby, {Whitney E} and Jouke-Jan Hottenga and Hongyan Huang and Jie Huang and Alicia Huerta-Chagoya and Huffman, {Jennifer E} and Yi-Jen Hung and Shaofeng Huo and Hwang, {Mi Yeong} and Hiroyuki Iha and Ikeda, {Daisuke D} and Masato Isono and Jackson, {Anne U} and Susanne J{\"a}ger and Jansen, {Iris E} and Ingegerd Johansson and Jonas, {Jost B} and Anna Jonsson and Torben J{\o}rgensen and Ioanna-Panagiota Kalafati and Masahiro Kanai and Stavroula Kanoni and K{\aa}rhus, {Line L} and Anuradhani Kasturiratne and Tomohiro Katsuya and Takahisa Kawaguchi and Kember, {Rachel L} and Kentistou, {Katherine A} and Han-Na Kim and Kim, {Young Jin} and Kleber, {Marcus E} and Knol, {Maria J} and Azra Kurbasic and Marie Lauzon and Phuong Le and Rodney Lea and Jong-Young Lee and Leonard, {Hampton L} and Li, {Shengchao A} and Xiaohui Li and Xiaoyin Li and Jingjing Liang and Honghuang Lin and Shih-Yi Lin and Jun Liu and Xueping Liu and Lo, {Ken Sin} and Jirong Long and Laura Lores-Motta and Jian'an Luan and Valeriya Lyssenko and Leo-Pekka Lyytik{\"a}inen and Anubha Mahajan and Vasiliki Mamakou and Massimo Mangino and Ani Manichaikul and Jonathan Marten and Manuel Mattheisen and Laven Mavarani and McDaid, {Aaron F} and Karina Meidtner and Melendez, {Tori L} and Mercader, {Josep M} and Yuri Milaneschi and Miller, {Jason E} and Millwood, {Iona Y} and Mishra, {Pashupati P} and Mitchell, {Ruth E} and M{\o}llehave, {Line T} and Anna Morgan and Soeren Mucha and Matthias Munz and Masahiro Nakatochi and Nelson, {Christopher P} and Maria Nethander and Nho, {Chu Won} and Nielsen, {Aneta A} and Nolte, {Ilja M} and Nongmaithem, {Suraj S} and Raymond Noordam and Ioanna Ntalla and Teresa Nutile and Anita Pandit and Paraskevi Christofidou and Katri P{\"a}rna and Marc Pauper and Petersen, {Eva R B} and Petersen, {Liselotte V} and Niina Pitk{\"a}nen and Ozren Pola{\v s}ek and Alaitz Poveda and Preuss, {Michael H} and Saiju Pyarajan and Raffield, {Laura M} and Hiromi Rakugi and Julia Ramirez and Asif Rasheed and Dennis Raven and Rayner, {Nigel W} and Carlos Riveros and Rebecca Rohde and Daniela Ruggiero and Ruotsalainen, {Sanni E} and Ryan, {Kathleen A} and Maria Sabater-Lleal and Richa Saxena and Markus Scholz and Anoop Sendamarai and Botong Shen and Jingchunzi Shi and Shin, {Jae Hun} and Carlo Sidore and Sitlani, {Colleen M} and Slieker, {Roderick C} and Smit, {Roelof A J} and Smith, {Albert V} and Smith, {Jennifer A} and Smyth, {Laura J} and Lorraine Southam and Valgerdur Steinthorsdottir and Liang Sun and Fumihiko Takeuchi and Tallapragada, {Divya Sri Priyanka} and Taylor, {Kent D} and Tayo, {Bamidele O} and Catherine Tcheandjieu and Natalie Terzikhan and Paola Tesolin and Alexander Teumer and Elizabeth Theusch and Thompson, {Deborah J} and Gudmar Thorleifsson and Timmers, {Paul R H J} and Stella Trompet and Constance Turman and Simona Vaccargiu and {van der Laan}, {Sander W} and {van der Most}, {Peter J} and {van Klinken}, {Jan B} and {van Setten}, Jessica and Verma, {Shefali S} and Niek Verweij and Yogasudha Veturi and Wang, {Carol A} and Chaolong Wang and Lihua Wang and Zhe Wang and Warren, {Helen R} and {Bin Wei}, Wen and Wickremasinghe, {Ananda R} and Matthias Wielscher and Wiggins, {Kerri L} and Winsvold, {Bendik S} and Andrew Wong and Yang Wu and Matthias Wuttke and Rui Xia and Tian Xie and Ken Yamamoto and Jingyun Yang and Jie Yao and Hannah Young and Yousri, {Noha A} and Lei Yu and Lingyao Zeng and Weihua Zhang and Xinyuan Zhang and Jing-Hua Zhao and Wei Zhao and Wei Zhou and Zimmermann, {Martina E} and Magdalena Zoledziewska and Adair, {Linda S} and Adams, {Hieab H H} and Aguilar-Salinas, {Carlos A} and Fahd Al-Mulla and Arnett, {Donna K} and Asselbergs, {Folkert W} and {\AA}svold, {Bj{\o}rn Olav} and John Attia and Bernhard Banas and Stefania Bandinelli and Bennett, {David A} and Tobias Bergler and Dwaipayan Bharadwaj and Ginevra Biino and Hans Bisgaard and Eric Boerwinkle and B{\"o}ger, {Carsten A} and Klaus B{\o}nnelykke and Boomsma, {Dorret I} and B{\o}rglum, {Anders D} and Borja, {Judith B} and Claude Bouchard and Bowden, {Donald W} and Ivan Brandslund and Ben Brumpton and Buring, {Julie E} and Caulfield, {Mark J} and Chambers, {John C} and Chandak, {Giriraj R} and Chanock, {Stephen J} and Nish Chaturvedi and Chen, {Yii-Der Ida} and Zhengming Chen and Ching-Yu Cheng and Christophersen, {Ingrid E} and Marina Ciullo and Cole, {John W} and Collins, {Francis S} and Cooper, {Richard S} and Miguel Cruz and Francesco Cucca and Cupples, {L Adrienne} and Cutler, {Michael J} and Damrauer, {Scott M} and Dantoft, {Thomas M} and {de Borst}, {Gert J} and {de Groot}, {Lisette C P G M} and {De Jager}, {Philip L} and {de Kleijn}, {Dominique P V} and {Janaka de Silva}, H and Dedoussis, {George V} and {den Hollander}, {Anneke I} and Shufa Du and Easton, {Douglas F} and Elders, {Petra J M} and Eliassen, {A Heather} and Ellinor, {Patrick T} and S{\"o}lve Elmst{\aa}hl and Jeanette Erdmann and Evans, {Michele K} and Diane Fatkin and Bjarke Feenstra and Feitosa, {Mary F} and Luigi Ferrucci and Ian Ford and Myriam Fornage and Andre Franke and Franks, {Paul W} and Freedman, {Barry I} and Paolo Gasparini and Christian Gieger and Giorgia Girotto and Goddard, {Michael E} and Golightly, {Yvonne M} and Clicerio Gonzalez-Villalpando and Penny Gordon-Larsen and Harald Grallert and Grant, {Struan F A} and Niels Grarup and Lyn Griffiths and Vilmundur Gudnason and Christopher Haiman and Hakon Hakonarson and Torben Hansen and Hartman, {Catharina A} and Hattersley, {Andrew T} and Caroline Hayward and Heckbert, {Susan R} and Chew-Kiat Heng and Christian Hengstenberg and Hewitt, {Alex W} and Haretsugu Hishigaki and Hoyng, {Carel B} and Huang, {Paul L} and Wei Huang and Hunt, {Steven C} and Kristian Hveem and Elina Hypp{\"o}nen and Iacono, {William G} and Sahoko Ichihara and Ikram, {M Arfan} and Isasi, {Carmen R} and Jackson, {Rebecca D} and Marjo-Riitta Jarvelin and Zi-Bing Jin and Karl-Heinz J{\"o}ckel and Joshi, {Peter K} and Pekka Jousilahti and Jukema, {J Wouter} and Mika K{\"a}h{\"o}nen and Yoichiro Kamatani and Kang, {Kui Dong} and Jaakko Kaprio and Kardia, {Sharon L R} and Fredrik Karpe and Norihiro Kato and Frank Kee and Thorsten Kessler and Khera, {Amit V} and Khor, {Chiea Chuen} and Kiemeney, {Lambertus A L M} and Bong-Jo Kim and Kim, {Eung Kweon} and Hyung-Lae Kim and Paulus Kirchhof and Mika Kivimaki and Woon-Puay Koh and Koistinen, {Heikki A} and Kolovou, {Genovefa D} and Kooner, {Jaspal S} and Charles Kooperberg and Anna K{\"o}ttgen and Peter Kovacs and Adriaan Kraaijeveld and Peter Kraft and Krauss, {Ronald M} and Meena Kumari and Zoltan Kutalik and Markku Laakso and Lange, {Leslie A} and Claudia Langenberg and Launer, {Lenore J} and {Le Marchand}, Loic and Hyejin Lee and Lee, {Nanette R} and Terho Lehtim{\"a}ki and Huaixing Li and Liming Li and Wolfgang Lieb and Xu Lin and Lars Lind and Allan Linneberg and Ching-Ti Liu and Jianjun Liu and Markus Loeffler and Barry London and Lubitz, {Steven A} and Lye, {Stephen J} and Mackey, {David A} and Reedik M{\"a}gi and Magnusson, {Patrik K E} and Marcus, {Gregory M} and Vidal, {Pedro Marques} and Martin, {Nicholas G} and Winfried M{\"a}rz and Fumihiko Matsuda and McGarrah, {Robert W} and Matt McGue and McKnight, {Amy Jayne} and Medland, {Sarah E} and Dan Mellstr{\"o}m and Andres Metspalu and Mitchell, {Braxton D} and Paul Mitchell and Mook-Kanamori, {Dennis O} and Morris, {Andrew D} and Mucci, {Lorelei A} and Munroe, {Patricia B} and Nalls, {Mike A} and Saman Nazarian and Nelson, {Amanda E} and Neville, {Matt J} and Christopher Newton-Cheh and Nielsen, {Christopher S} and N{\"o}then, {Markus M} and Claes Ohlsson and Oldehinkel, {Albertine J} and Lorena Orozco and Katja Pahkala and P{\"a}ivi Pajukanta and Palmer, {Colin N A} and Parra, {Esteban J} and Cristian Pattaro and Oluf Pedersen and Pennell, {Craig E} and Penninx, {Brenda W J H} and Louis Perusse and Annette Peters and Peyser, {Patricia A} and Porteous, {David J} and Danielle Posthuma and Chris Power and Pramstaller, {Peter P} and Province, {Michael A} and Qibin Qi and Jia Qu and Rader, {Daniel J} and Raitakari, {Olli T} and Sarju Ralhan and Rallidis, {Loukianos S} and Rao, {Dabeeru C} and Susan Redline and Reilly, {Dermot F} and Reiner, {Alexander P} and Rhee, {Sang Youl} and Ridker, {Paul M} and Michiel Rienstra and Samuli Ripatti and Ritchie, {Marylyn D} and Roden, {Dan M} and Rosendaal, {Frits R} and Rotter, {Jerome I} and Igor Rudan and Femke Rutters and Charumathi Sabanayagam and Danish Saleheen and Veikko Salomaa and Samani, {Nilesh J} and Sanghera, {Dharambir K} and Naveed Sattar and B{\"o}rge Schmidt and Helena Schmidt and Reinhold Schmidt and Schulze, {Matthias B} and Heribert Schunkert and Scott, {Laura J} and Scott, {Rodney J} and Peter Sever and Shiroma, {Eric J} and Shoemaker, {M Benjamin} and Xiao-Ou Shu and Simonsick, {Eleanor M} and Mario Sims and Singh, {Jai Rup} and Singleton, {Andrew B} and Sinner, {Moritz F} and Smith, {J Gustav} and Harold Snieder and Spector, {Tim D} and Stampfer, {Meir J} and Stark, {Klaus J} and Strachan, {David P} and {'t Hart}, {Leen M} and Yasuharu Tabara and Hua Tang and Jean-Claude Tardif and Thanaraj, {Thangavel A} and Timpson, {Nicholas J} and Anke T{\"o}njes and Angelo Tremblay and Tiinamaija Tuomi and Jaakko Tuomilehto and Maria-Teresa Tusi{\'e}-Luna and Uitterlinden, {Andre G} and {van Dam}, {Rob M} and {van der Harst}, Pim and {Van der Velde}, Nathalie and {van Duijn}, {Cornelia M} and {van Schoor}, {Natasja M} and Veronique Vitart and Uwe V{\"o}lker and Peter Vollenweider and Henry V{\"o}lzke and Wacher-Rodarte, {Niels H} and Mark Walker and Wang, {Ya Xing} and Wareham, {Nicholas J} and Watanabe, {Richard M} and Hugh Watkins and Weir, {David R} and Werge, {Thomas M} and Elisabeth Widen and Wilkens, {Lynne R} and Gonneke Willemsen and Willett, {Walter C} and Wilson, {James F} and Tien-Yin Wong and Jeong-Taek Woo and Wright, {Alan F} and Jer-Yuarn Wu and Huichun Xu and Yajnik, {Chittaranjan S} and Mitsuhiro Yokota and Jian-Min Yuan and Eleftheria Zeggini and Zemel, {Babette S} and Wei Zheng and Xiaofeng Zhu and Zmuda, {Joseph M} and Zonderman, {Alan B} and John-Anker Zwart and Chasman, {Daniel I} and Cho, {Yoon Shin} and Heid, {Iris M} and McCarthy, {Mark I} and Ng, {Maggie C Y} and O'Donnell, {Christopher J} and Fernando Rivadeneira and Unnur Thorsteinsdottir and Sun, {Yan V} and Tai, {E Shyong} and Michael Boehnke and Panos Deloukas and Justice, {Anne E} and Lindgren, {Cecilia M} and Loos, {Ruth J F} and Mohlke, {Karen L} and North, {Kari E} and Kari Stefansson and Walters, {Robin G} and Winkler, {Thomas W} and Young, {Kristin L} and Po-Ru Loh and Jian Yang and T{\~o}nu Esko and Assimes, {Themistocles L} and Adam Auton and Abecasis, {Goncalo R} and Willer, {Cristen J} and Locke, {Adam E} and Berndt, {Sonja I} and Guillaume Lettre and Frayling, {Timothy M} and Yukinori Okada and Wood, {Andrew R} and Visscher, {Peter M} and Hirschhorn, {Joel N} and {23Andme Research Team}",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = oct,
doi = "10.1038/s41586-022-05275-y",
language = "English",
volume = "610",
pages = "704--712",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7933",
}